Queensland Brain Institute 2010 Annual Report - University of ...

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Laboratory Head Dr Timothy BredyDr Timothy Bredy’s laboratory is interested in elucidating how the genomeis connected to the environment, and how this relationship shapes brainand behaviour across the lifespan. In contrast to the information conveyedby a static genome, the epigenome is very dynamic and can be modifiedby exposure to a variety of environmental stimuli, including learning,exposure to drugs of abuse, environmental toxins, dietary factors andsocial interaction.1Original Memory2Memory RetrievalNewInformationPG | 28Above: Bredy group photo. 2010 Laboratory Members: Kevin Dudley, Carlos Coelho, Wei Wei, Xiang Li , Danay Baker-Andresen, Vikram Ratnu, RogerMarek, Zoran Boskovic, Maria Galeanos, Joanne Loh, Zhanzhi Yan. Above right: The transcription factor ATF4 is coexpressed with the histoneacetyltransferase PCAF within the infralimbic prefrontal cortex.Shaping scientific understanding of epigenetic mechanismsIn 2010, the Bredy group discovered that, inmice, the extinction of conditional fear (aform of inhibitory learning important for thetreatment of anxiety disorders) is regulated bymicroRNA activity in the prefrontal cortex. Wealso demonstrated that there are epigeneticregulatory proteins such as p300/CBP-associatedfactor (PCAF), which are unique to theextinction learning process. We have alsobeen performing genome-wide methylationprofiling experiments to determine whethersex-specific cortical DNA methylationpatterns are associated with sex differences infear-related learning and memory.The year has been a busy one in otherways. Laboratory members organised thefirst Epigenetics, Behaviour and Diseasesymposium, while Dr Bredy delivered invitedtalks at a range of neuroscience events. DrBredy and Dr Kevin Dudley, a postdoctoralfellow, published a review on epigeneticmechanisms mediating vulnerability andresilience to psychiatric disorders.In December, the group welcomed PhDcandidate Ms Danay Baker-Andresen, whoholds a National Science and EngineeringCouncil post-graduate scholarship, fromCanada. We were fortunate to host a summerresearch scholar, Mr Xiang Li, and we alsowelcomed two co-supervised PhD students –Mr Vikram Ratnu with Professor John Mattick,and Mr Roger Marek with Professor PankajSah.Our research associates, Drs Wei Wei and CarlosCoelho, continued to perform extraordinarilyin overseeing experiments and maintainingthe laboratory. Lastly, with the support of anARC LIEF grant, we began working towardsestablishing a mass spectrometry core facilityat QBI, and optimizing new technologyfor epigenetic profiling using the IlluminaHiSeq2000 platform.34Destabilization ofOriginal MemorymiRNAActivityNew, updated MemoryMiRNAs may regulate neural plasticityand memory by constraining ordestabilising memory upon retrievalin order to allow new learning ormemory updating to occur.
Queensland Brain Institute Annual Report 2010Laboratory Head Dr Thomas BurneThe Burne laboratory studies brain development and behaviour in animalmodels to learn more about neuropsychiatric diseases. Researchersinvestigate the underlying biological basis for schizophrenia, with the aimof finding appropriate public health interventions. The group has beenexploring the impact of developmental vitamin D deficiency on braindevelopment, the impact of adult vitamin D deficiency on brain functionand behaviour, and the neurobiological effects of having an older father.The group is part of the Queensland Centre for Mental Health Research.Above right: Burne group photo. 2010 Laboratory Members: James Kesby, Lauren Harms, Claire Foldi, Carlie Cullen, Natalie Groves, Karly Turner,Suzy Alexander, Meggie Voogt, Pauline Ko, Henry Simila. Above left: Claire Foldi analyses magnetic resonance images of a mouse brain.Dr James Kesby measuresneurotransmitters in samples frombrain tissueIn 2010, the Burne group, in collaborationwith QBI’s Dr Darryl Eyles and ProfessorJohn McGrath, built on its previous researchshowing that low levels of vitamin D (the‘sunshine hormone’) in the prenatal period isassociated with an increased risk of schizophrenia.This work was published in theArchives of General Psychiatry. We haveexplored the behaviour, brain neurochemistryand receptor profile associated with vitaminD deficiency in animal models. Now the collaborationis investigating the impact of DVDdeficiency on social and cognitive behaviours.Probing the roots of schizophreniaResearch into the impact of adult vitamin Ddeficiency on brain function has also started.The Burne group has also expanded itsresearch tools, with a suite of cognitivebehavioural tasks to assess attentionalprocessing in rodents. The goal now is toinvestigate the neurobiology of alteredcognition in animal models, by looking atselected cognitive domains – sensorimotorgating, working memory, attention andspeed of processing, learning and memory,and problem solving – that are known to bedisrupted in schizophrenia. In collaborationwith other neuroscientists at QBI, we havealso begun to incorporate other species, suchas zebrafish and fruit flies, to ask questions ofthe ‘small brain’. This research made the coverof Molecular Psychiatry.Further, the group published the first comprehensivestudy of the impact of advancedpaternal age in a mouse model on behaviourand brain structure. In collaboration withresearchers at the Queensland Instituteof Medical Research, explorations intobehavioural, genomic and brain imaging in amouse model are now underway.PG | 29
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